A very simple model system, the cellular slime mold Dictyostelim discoideum, is being used to study mechanisms which control developmental gene activation during normal differentiation. Post-aggregation Dictyostelium cells transcribe an additional 26% of their genome which is not expressed in earlier preaggregation stage cells. Studies designed to identify factors which regulate the coordinate expression of this large portion of the genome indicate that cell-cell interaction is a necessary prerequisite for both the synthesis and stability of the late mRNAs. Disruption of cell contacts results in the rapid and specific degradation of the late mRNA species. Messenger RNA species whose expression is conserved throughout development are unaffected by disaggregation. Addition of cyclic AMP to cells which have been disaggregated restores the level of most, but not all, of the late mRNAs. Thus, an event which initiates at the cell surface brings about a change in the nucleus which allows the transcription of an additional 26% of the Dictyostelium single copy genome. The actual rate of transcription and the subsequent stability of many of the mRNAs transcribed off of this portion of the genome are then further regulated by a cyclic AMP mediated process.